The use of an individual's genetic information in the diagnosis of a disease is becoming more prevalent. Many diseases are caused by a defect in a single gene of an individual. All known autosomal dominant, autosomal recessive and X-linked disorders are believed to be caused by a defect in a single gene (Antonarakis, New England Journal of Medicine Vol. 320, No. 3:153-63 (1981)). Genes responsible for some diseases or disorders have been cloned and characterized. The defect in the gene may be a gross gene alteration, a small gene alteration or even a point mutation. Examples of some diseases caused by a mutation in a gene include Gaucher's disease, hemophelia A and B, Duchenne's muscular dystrophy, sickle cell anemia, Tay-Sachs disease, phenylketonoria and cystic fibrosis.
Familial hypertrophic cardiomyopathy (hereinafter FHC) has been linked to mutations in the .beta. cardiac myosin heavy-chain gene (Tanigawa et al., Cell 62:991-998 (1990)); Geisterfer-Lowrance et al., Cell 61:999-1006 (1990)). Tanigawa et al. studied a single family (Family B) and hypothesized that the FHC in this family was due to a mutation that results in the formation of an .alpha./.beta. cardiac myosin heavy-chain hybrid gene. Geisterfer-Lowrance et al. also studied a single family and hypothesized that a missense mutation in the .beta. cardiac myosin heavy-chain gene caused FHC in the family studied.
FHC is a well characterized autosomal dominant disorder or disease. It is autosomal dominant in that fifty percent of the children of affected parents eventually become afflicted with the disease. FHC is characterized by unexplained myocardial hypertrophy. The clinical symptoms of individuals having FHC are variable and some individuals do not have any symptoms. The symptoms of FHC include dypsnea, angina, ischemia. Pathological findings of the disease include increased myocardial mass with myocyte and myofibrillar disarray.
Presently, the diagnosis of individuals having FHC relies on the presence of typical clinical symptoms and the demonstration of unexplained ventricular hypertrophy. Sudden, unexpected death is the most serious consequence of FHC. Sudden death occurs in both symptomatic and asymptomatic individuals and FHC has an annual mortality of approximately four percent from sudden death.